Low-Cost 3D Models for Cervical Spine Tumor Removal Training for Neurosurgery Residents.

BACKGROUND AND OBJECTIVES: Spinal surgery, particularly for cervical pathologies such as myelopathy and radiculopathy, requires a blend of theoretical knowledge and practical skill. The complexity of these conditions, often necessitating surgical intervention, underscores the need for intricate understanding and precision in execution. Advancements in neurosurgical training, especially with the use of low-cost 3D models for simulating cervical spine tumor removal, are revolutionizing this field. These models provide the realistic and hands-on experience crucial for mastering complex neurosurgical techniques, filling gaps left by traditional educational methods. MATERIALS AND METHODS: This study aimed to assess the effectiveness of 3D-printed cervical vertebrae models in enhancing surgical skills, focusing on tumor removal, and involving 20 young neurosurgery residents. These models, featuring silicone materials to simulate the spinal cord and tumor tissues, provided a realistic training experience. The training protocol included a laminectomy, dural incision, and tumor resection, using a range of microsurgical tools, focusing on steps usually performed by senior surgeons. RESULTS: The training program received high satisfaction rates, with 85% of participants extremely satisfied and 15% satisfied. The 3D models were deemed very realistic by 85% of participants, effectively replicating real-life scenarios. A total of 80% found that the simulated pathologies were varied and accurate, and 90% appreciated the models' accurate tactile feedback. The training was extremely useful for 85% of the participants in developing surgical skills, with significant post-training confidence boosts and a strong willingness to recommend the program to peers. CONCLUSIONS: Continuing laboratory training for residents is crucial. Our model offers essential, accessible training for all hospitals, regardless of their resources, promising improved surgical quality and patient outcomes across various pathologies.

Effect of M-wave Amplitude on Inter-evaluator Concordance and Number of Detected Innervation Zones in the Medial Gastrocnemius Using Multichannel Electromyography / Efecto de la Amplitud de la Onda M sobre la Concordancia entre Evaluadores y el Número de Zonas de Inervación Detectadas en el Gastrocnemio Medial Mediante Electromiografía Multicanal

SUMMARY: The Innervation Zones (IZ) correspond to clusters of neuromuscular junctions. The traditional method of locating IZs through voluntary muscle contractions may not be feasible in individuals with motor disorders. Imposed contractions by electrostimulation are an alternative. However, there is limited evidence regarding the factors that affect inter-evaluator concordance and the number of localized IZs when using imposed contraction. The main objective of this research was to determine the effect of the amplitude of compound motor action potentials (CMAPs) containing the M-wave on inter-evaluator agreement. As a secondary objective, was investigate the effect on the number of detected IZs. Twenty-four healthy volunteers (age: 21.2 ± 1.5years, weight: 67.4 ± 13.2kg, height: 1.68 ± 0.80m) participated in the study. Electrostimulation was applied to the tibial nerve to induce contraction of the medial gastrocnemius. The IZ were identified based on the M-wave recorded through multichannel electromyography. A receiver operating characteristic (ROC) analysis was conducted to assess sensitivity and specificity in detecting the IZs. Inter-rater agreement was evaluated using a two-way mixed effects test to determine the intraclass correlation coefficients (ICC). A p-value less than 0.05 was considered statistically significant. The ROC analysis revealed that for both evaluators, a specificity of 95% was achieved with an amplitude ≥30 %. The area under the ROC curve was 0.980 [0.964, 0.996], indicating a strong influence of CMAP amplitude on detection of IZs. The highest level of agreement (ICC = 0.788 [0.713, 0.844]) among the evaluators was observed with CMAP amplitudes equal to or greater than 80 % of the maximum M-wave. The findings of this study demonstrate that both the number and the inter-evaluator concordance for detecting IZs using imposed contractions are strongly influenced by the amplitude of the M-wave. Higher M-wave amplitudes were associated with improved concordance and increased IZ detection, making it crucial to standardize amplitude settings for reliable outcomes.

Las Zonas de Inervación (IZ) corresponden a grupos de uniones neuromusculares. El método tradicional para localizar IZs mediante contracciones musculares voluntarias puede no ser factible en personas con trastornos motores. Las contracciones impuestas mediante electro estimulación son una alternativa. Sin embargo, existe poca evidencia sobre los factores que afectan la concordancia entre evaluadores y el número de IZs localizadas al usar este tipo de contracciones. El objetivo de esta investigación fue determinar el efecto de la amplitud de los potenciales de acción motores compuestos (PAMCs) que contienen la onda M sobre la concordancia entre evaluadores. Como objetivo secundario, se investigó el efecto sobre el número de IZs detectadas. Veinticuatro voluntarios sanos (edad: 21.2 ± 1.5 años, peso: 67.4 ± 13.2 kg, altura: 1.68 ± 0.80 m) participaron en el estudio. Se aplicó electroestimulación al nervio tibial para inducir la contracción del gastrocnemio medial. Las IZs se identificaron según la onda M registrada mediante electromiografía multicanal. Se realizó un análisis de curva de las característica del receptor (ROC) para evaluar la sensibilidad y especificidad en la detección de las IZs. La concordancia entre evaluadores se evaluó utilizando una prueba de efectos mixtos de dos vías para determinar los coeficientes de correlación intraclase (ICC). Se consideró un valor de p menor que 0.05 como estadísticamente significativo. El análisis ROC reveló que para ambos evaluadores se logró una especificidad del 95% con una amplitud ≥30 %. El área bajo la curva ROC fue de 0.980 [0.964, 0.996], lo que indica una fuerte influencia de la amplitud del CMAP en la detección de las IZs. El nivel más alto de concordancia (ICC = 0.788 [0.713, 0.844]) entre los evaluadores se observó con amplitudes de CMAP iguales o mayores al 80 % de la onda M máxima. Los hallazgos de este estudio demuestran que tanto el número como la concordancia entre evaluadores para detectar IZs mediante contracciones impuestas están fuertemente influenciados por la amplitud de la onda M. Las amplitudes más altas de la onda M se asociaron con una concordancia mejorada y un aumento en la detección de IZs, lo que hace crucial estandarizar los ajustes de amplitud para obtener resultados confiables.

Identity-by-descent analysis of a large Tourette's syndrome pedigree from Costa Rica implicates genes involved in neuronal development and signal transduction.

Tourette Syndrome (TS) is a heritable, early-onset neuropsychiatric disorder that typically begins in early childhood. Identifying rare genetic variants that make a significant contribution to risk in affected families may provide important insights into the molecular aetiology of this complex and heterogeneous syndrome. Here we present a whole-genome sequencing (WGS) analysis from the 11-generation pedigree (>500 individuals) of a densely affected Costa Rican family which shares ancestry from six founder pairs. By conducting an identity-by-descent (IBD) analysis using WGS data from 19 individuals from the extended pedigree we have identified putative risk haplotypes that were not seen in controls, and can be linked with four of the six founder pairs. Rare coding and non-coding variants present on the haplotypes and only seen in haplotype carriers show an enrichment in pathways such as regulation of locomotion and signal transduction, suggesting common mechanisms by which the haplotype-specific variants may be contributing to TS-risk in this pedigree. In particular we have identified a rare deleterious missense variation in RAPGEF1 on a chromosome 9 haplotype and two ultra-rare deleterious intronic variants in ERBB4 and IKZF2 on the same chromosome 2 haplotype. All three genes play a role in neurodevelopment. This study, using WGS data in a pedigree-based approach, shows the importance of investigating both coding and non-coding variants to identify genes that may contribute to disease risk. Together, the genes and variants identified on the IBD haplotypes represent biologically relevant targets for investigation in other pedigree and population-based TS data.

Generation of an induced pluripotent stem cell line NCHi003-A from a 11-year-old male with pulmonary atresia with intact ventricular septum (PA-IVS).

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital heart defect defined by membranous or muscular atresia of the right ventricular outflow tract where patients display varying degrees of hypoplasia of the right ventricle. This condition results in cyanosis due to an inability of blood to flow from the right ventricle to the pulmonary arteries, thus requiring immediate surgical intervention after birth. An iPSC line was generated from peripheral blood mononuclear cells of a 11-year-old male patient diagnosed with PA-IVS through Sendai virus-mediated reprogramming. This disease-specific iPSC line was characterized by immunocytochemistry, STR analysis, karyotype analysis, and mycoplasma testing.

Characterization of an iPSC line NCHi006-A from a patient with hypoplastic left heart syndrome (HLHS).

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect characterized by underdeveloped structures on the left side of the heart, including hypoplasia of the left ventricle and stenosis or atresia of the aortic and mitral valves. Here, we generated an iPSC line from the peripheral blood mononuclear cells of a male patient with HLHS through Sendai virus-mediated transfection of 4 Yamanaka factors. This iPSC line exhibited normal morphology, expressed pluripotency markers, had a normal karyotype, and could differentiate into cells of three germ layers. This iPSC line can be used for studying cellular and developmental etiologies of HLHS.

Effect of the SARS-CoV-2 pandemic on the control and severity of pediatric asthma

Background: The novel disease caused by the new coronavirus SARS-CoV-2 has caused an unprecedented global pandemic. Care providers of asthmatic children are increasingly con-cerned; as viral infections are one of the primary triggers of asthma flare-up. However, the effect of SARS-CoV-2 as well as the generated worldwide lockdown on asthmatic children is unknown.Objective: The aim of this study was to analyze the effects of pandemic SARS-CoV-2 in pediat-ric asthma control.Material and Methods: A retrospective, open, transversal study was performed at five ter-tiary hospitals. Recruited patients were aged <18 years and had physician-diagnosed asthma. Information regarding the 2019 and 2020 seasons were provided.Results: Data were collected from 107 children (age range: 3–18 years, mean age: 12 years). Well-controlled asthma was observed in 58 (54.2%) patients in 2020 versus 30 (28%) in 2019, and 15 (14%) patients had poorly controlled asthma in 2020 versus 28 (26.2%) in 2019. In 2020, a decrease in exacerbations caused by allergies to pollen, dust mites, molds, and through other causes not related to SARS-CoV-2 infection was observed. An increase in exacerbations was observed due to animal dander, stress, physical exercise, and SARSCoV-2 infection. Children had a reduced need for asthma-controlling medication, made fewer visits to healthcare providers and had lesser need of treatment with oral corticosteroids if compared with the same season of 2019 (AU)

Effect of the SARS-CoV-2 pandemic on the control and severity of pediatric asthma.

BACKGROUND: The novel disease caused by the new coronavirus SARS-CoV-2 has caused an unprecedented global pandemic. Care providers of asthmatic children are increasingly con-cerned; as viral infections are one of the primary triggers of asthma flare-up. However, the effect of SARS-CoV-2 as well as the generated worldwide lockdown on asthmatic children is unknown. OBJECTIVE: The aim of this study was to analyze the effects of pandemic SARS-CoV-2 in pediat-ric asthma control. MATERIAL AND METHODS: A retrospective, open, transversal study was performed at five ter-tiary hospitals. Recruited patients were aged <18 years and had physician-diagnosed asthma. Information regarding the 2019 and 2020 seasons were provided. RESULTS: Data were collected from 107 children (age range: 3-18 years, mean age: 12 years). Well-controlled asthma was observed in 58 (54.2%) patients in 2020 versus 30 (28%) in 2019, and 15 (14%) patients had poorly controlled asthma in 2020 versus 28 (26.2%) in 2019. In 2020, a decrease in exacerbations caused by allergies to pollen, dust mites, molds, and through other causes not related to SARS-CoV-2 infection was observed. An increase in exacerbations was observed due to animal dander, stress, physical exercise, and SARSCoV-2 infection. Children had a reduced need for asthma-controlling medication, made fewer visits to healthcare providers and had lesser need of treatment with oral corticosteroids if compared with the same season of 2019. CONCLUSION: Pediatric asthma control improved, the need for controller medication declined, and fewer visits to healthcare providers were made during the pandemic if compared with the 2019 season.

Urate levels and clearance in renal patients under peritoneal dialysis.

Hemodialysis adequately controls serum uric acid (UA) levels, making UA-lowering drugs unnecessary; scant data are available for peritoneal dialysis (PD). We analyzed blood, 24 h urine and dialysis fluid from twenty patients under PD, to assess UA levels and clearances, and factors associated with better performance and maintenance of target levels (<6mg/dL). Median serum UA was 5.4 mg/dL (p25-75 4.4-5.8), mainly achieved through peritoneal clearance (3.0 mL/min/1.73m2, 71.2% of total UA clearance); 75% of participants was on UA targets. Continuous cycling peritoneal dialysis showed highest UA clearance and target achievements. These findings may be of interest for end-stage renal patients with gout.

Genetic Overlap Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multisite Study of Multiplex Pedigrees.

BACKGROUND: Cognitive impairment is a key feature of psychiatric illness, making cognition an important tool for exploring of the genetics of illness risk. It remains unclear which measures should be prioritized in pleiotropy-guided research. Here, we generate profiles of genetic overlap between psychotic and affective disorders and cognitive measures in Caucasian and Hispanic groups. METHODS: Data were from 4 samples of extended pedigrees (N = 3046). Coefficient of relationship analyses were used to estimate genetic overlap between illness risk and cognitive ability. Results were meta-analyzed. RESULTS: Psychosis was characterized by cognitive impairments on all measures with a generalized profile of genetic overlap. General cognitive ability shared greatest genetic overlap with psychosis risk (average endophenotype ranking value [ERV] across samples from a random-effects meta-analysis = 0.32), followed by verbal memory (ERV = 0.24), executive function (ERV = 0.22), and working memory (ERV = 0.21). For bipolar disorder, there was genetic overlap with processing speed (ERV = 0.05) and verbal memory (ERV = 0.11), but these were confined to select samples. Major depressive disorder was characterized by enhanced working and face memory performance, as reflected in significant genetic overlap in 2 samples. CONCLUSIONS: There is substantial genetic overlap between risk for psychosis and a range of cognitive abilities (including general intelligence). Most of these effects are largely stable across of ascertainment strategy and ethnicity. Genetic overlap between affective disorders and cognition, on the other hand, tends to be specific to ascertainment strategy, ethnicity, and cognitive test battery.

An Individual Patient Data Meta-Analysis with Colombian Studies on the Effect of Dark Chocolate Consumption on Cardiovascular Risk Parameters.

BACKGROUND: It is postulated that cocoa solids possess cardioprotective capacity by various mechanisms. In the different cocoa studies evaluating cardiovascular disease, there are no conclusive data on the role it plays in controlling the lipid profile and anthropometric variables, perhaps because the concentration of cocoa, the geographical origin of the population, and the different concentrations supplied lead to a high heterogeneity of results. This study aims to estimate the effect of consuming cocoa-rich chocolate compared to placebo on the lipid profile and anthropometric variables based on data from three clinical trials conducted in Colombia. METHODS: Meta-analysis of individual data from three randomized clinical trials conducted in Colombia. The entire population of the primary studies was included, which was reassigned into intervention groups if they consumed 50 grams of 70% concentrated cocoa or placebo, which was considered to be cocoa-free or with a concentration less than 50 grams. The variables at the beginning of the study were analyzed with medians, interquartile ranges, means, and deviations according to whether they met the normality assumption. Multiple imputations were used to manage missing data and were analyzed using the two approaches proposed for this type of study, that of one and two stages. In the two-stage approach, the data were weighted on a conventional Forrest plot, while in the one-stage approach, linear regressions with mixed models were applied. This study is governed by the regulations described in the 2013 Declaration of Helsinki and by article 11 of Resolution 8430 of 1993, which classifies it as a risk-free study. RESULTS: A total of 275 participants were included, who consumed cocoa or placebo for 81 days on average; 52.7% were female and few smoked at the time of the intervention (31/275). Physical activity performed in number of hours per week was comparable between the intervention groups. When evaluating total cholesterol, low-density cholesterol (LDL), high-density cholesterol (HDL), triglycerides, abdominal circumference, and final body mass index with both the one-stage and two-stage approaches, there were no significant differences between the two groups. CONCLUSIONS: According to the results obtained in the meta-analysis, the consumption of cocoa in the Colombian population does not seem to significantly modify variables such as lipid profile, abdominal circumference, and body mass index. This conclusion according to the quality of the evidence has a weak recommendation and a low-to-moderate certainty. However, the analysis through the two proposed approaches yielded similar results.

Underlying domains of anxiety trait in a Costa Rican sample: preliminary results.

BACKGROUND: Imprecision of the psychiatric phenotype might partially explain the failure of genetic research to identify genes that contribute to susceptibility of anxiety disorders. Previous research concluded two underlying constructs, worry and rumination, might explain anxiety sub-syndromic symptoms in Costa Rican patients with history of mania. The goal of the current study is to explore the presence of latent constructs for quantitative anxiety in a group of subjects with a wide diagnostic phenotype and non-affected individuals. METHODS: We conducted an exploratory factor analysis of anxiety trait in 709 subjects. Our sample was comprised by 419 subjects with psychiatric disorders and 290 non-affected individuals. We used principal factors extraction method with squared multiple correlations of the STAI (trait subscale). RESULTS: We found the following preliminary results: a three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.92 (>0.6) and Bartlett's Test of Sphericity of 5644,44 (p<0.05). The STAI items were grouped into three factors: anxiety-absent, worry and rumination based on the characteristics of the symptoms. CONCLUSION: Two underlying constructs, worry and rumination may explain anxiety sub-syndromic symptoms in Costa Rican subjects. Our proposed underlying structure of subsyndromal anxiety in individuals should be considered as an important factor in defining better phenotypic characterizations on a broader diagnostic concept. Worry and rumination as a phenotypic characterization may assist in genotyping; however, its predictive value on actual illness outcome still requires more research. The Genome-Wide QTL analysis for anxiety trait in the same sample is ongoing.

Envarsus, una novedad para los nefrólogos del trasplante: estudio observacional retrospectivo / Envarsus, a novelty for transplant nephrologists: Observational retrospective study

El objetivo del presente estudio fue evaluar las concentraciones valle (Cpvalle) y la pauta posológica de tacrolimus tras la conversión de Prograf o Advagraf a Envarsus (nueva forma farmacéutica con tecnología Meltdose que mejora la absorción de fármacos liposolubles) en pacientes con trasplante renal estable, y su función renal. Se seleccionaron los pacientes trasplantados renales estables que fueron convertidos a Envarsus. Se definieron dos periodos: basal y conversión (Envarsus), y se estratificaron en función de la forma farmacéutica utilizada en el periodo basal. Se incluyeron 61 pacientes (24 con Advagraf y 37 con Prograf), con una edad media de 52 años. El tiempo medio postrasplante en el momento de la conversión a Envarsus fue de 76,3 meses y el seguimiento medio en el periodo basal y conversión fue de 10,1 y 11,6 meses, respectivamente. En el grupo Prograf y Envarsus las medianas Cpvalle fueron 6,6 vs 6,4 ng/ml (p = 0,636), con una dosis diaria media que disminuyó significativamente de 3 a 2 mg (p < 0,001), respectivamente, manteniendo el filtrado renal. Las medianas Cpvalle en los grupos Advagraf y Envarsus fueron 5,7 y 6,3 ng/ml (p = 0,07), con una mediana de dosis diaria de 7 y 4 mg (p < 0,001), respectivamente, e igual función renal. En pacientes trasplantados renales estables la conversión de Advagraf a Envarsus ha permitido reducir la dosis de tacrolimus un 42,9% y la de Prograf un 33,3% para mantener unas Cpvalle similares, sin que se altere la función renal

The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function. We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52 years. The mean post-transplant time at the time of conversion to Envarsus was 76.3 months and the mean follow-up in the Baseline and Conversion period was 10.1 months and 11.6 months, respectively. In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/mL (P = .636), with a mean daily dose that decreased significantly from 3 mg to 2 mg (P < .001), respectively, maintaining the filtration rate. The median Cptrough values in the Advagraf and Envarsus groups were 5.7 ng/mL and 6.3 ng/mL (P=.07), with a median daily dose of 7 mg and 4 mg (P<.001), respectively, and the same renal function. In stable renal transplant patients, the conversion from Advagraf to Envarsus has allowed the dose of tacrolimus to be reduced by 42.9% and, in the case of Prograf, by 33.3%, maintaining similar Cptrough values, without renal function being altered

Chipless-RFID: A Review and Recent Developments.

In this paper, a review of the state-of-the-art chipless radiofrequency identification (RFID) technology is carried out. This recent technology may provide low cost tags as long as these tags are not equipped with application specific integrated circuits (ASICs). Nevertheless, chipless-RFID presents a series of technological challenges that have been addressed by different research groups in the last decade. One of these challenges is to increase the data storage capacity of tags, in order to be competitive with optical barcodes, or even with chip-based RFID tags. Thus, the main aim of this paper is to properly clarify the advantages and disadvantages of chipless-RFID technology. Moreover, since the coding information is an important aspect in such technology, the different coding techniques, as well as the main figures of merit used to compare different chipless-RFID tags, will be analyzed.

Differential Microfluidic Sensors Based on Dumbbell-Shaped Defect Ground Structures in Microstrip Technology: Analysis, Optimization, and Applications.

A microstrip defect ground structure (DGS) based on a pair of dumbbell-shaped slots is used for sensing. The device is a differential sensor consisting of a pair of mirrored lines loaded with a dumbbell-shaped DGS, and the output variable is the cross-mode transmission coefficient. Such a variable is very sensitive to asymmetries in the line pair, e.g., caused by an asymmetric dielectric load in the dumbbell-shaped DGSs. Therefore, the sensor is of special interest for the dielectric characterization of solids and liquids, or for the measurement of variables related to complex permittivity changes. It is shown in this work that by adding fluidic channels on top of the dumbbell-shaped DGSs, the device is useful for liquid characterization, particularly for the measurement of solute concentration in very diluted solutions. A sensitivity analysis useful for sensor design is carried out in this paper.

Expression of estrogen receptor beta (ERß) and its prognostic value in pleural mesothelioma.

BACKGROUND: Overexpression of estrogen receptors in malignant pleural mesothelioma has shown an independent relation with a better prognosis of survival, and the use of selective estrogen receptor beta (ERß) agonists increases the susceptibility to antitumor treatment. METHODS: This was a retrospective single center study that analyzed the response of malignant pleural mesothelioma with an expression of ERß to first-line chemotherapy. The study included patients with pleural mesothelioma pathologically confirmed between 2013 and 2016 at the National Institute for Respiratory Disease (INER), who underwent an immunohistochemistry assay for ERß (mouse monoclonal antibody PPG5/10). The primary endpoint was the response to chemotherapy based on RECIST 1.1 according to the ERß expression; secondary outcomes were the overall survival (OS) and progression-free survival (PFS). RESULTS: We included 22 patients, regarding the expression of ERß, 17 (77.2%) patients had high or moderate degree, while 5 (22.7%) had low degree or null expression. The response to treatment as by RECIST 1.1, 12 (54.5%) had partial response, 5 (22.7%) had stable disease, and 3 (13.6%) had progression. None of the patients had a complete response. Of those who had a partial response, 9 (75%) had a high or moderate degree of ERß expression in tumor cells, and 3 (25%) had a low or null degree of expression. CONCLUSIONS: High and moderate expression of ERß group with advanced clinical stage malignant pleural mesothelioma was associated with a tendency of higher OS and better response to chemotherapy treatment resulting in longer PFS although statistical significance was not achieved.

Un cuarto de siglo de investigación genética en los trastornos neuropsiquiátricos en Costa Rica

El estudio de la base genética de los trastornos neuropsiquiátricos se inició en Costa Rica hace más de 25 años. En este tiempo se han realizado investigaciones enfocadas en diferentes trastornos: esquizofrenia, trastorno bipolar, demencia de Alzheimer, trastorno obsesivo compulsivo, trastorno obsesivo compulsivo, trastorno por déficit de atención y síndrome de Tourette. Los estudios realizados han tenido una amplia variación en lo que se refiere a diseño (ligamiento/asociación), muestra utilizada (familias/parejas de hermanos afectados/tríos), cobertura genómica (estudios con genes candidatos/tamizajes de todo el genoma) y definición del fenotipo (categoría diagnóstica/clasificación sindrómica/endofenotipo). Presentamos un resumen de los principales hallazgos genómicos obtenidos en estos estudios multidisciplinarios y discutimos la importancia, lecciones y retos de la investigación genética en trastornos psiquiátricos complejos.

In Costa Rica, the study of the genetic basis of neuropsychiatric disorders started more than 25 years ago. During this time, different research efforts have focused on several disorders: schizophrenia, bipolar disorder, Alzheimer's disease, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, and Tourette syndrome. The studies have had a wide scope regarding design (linkage/association), sample used (families/sib pairs/trios), genome coverage (candidate gene studies/genome-wide scans), and phenotype definition (diagnostic category/syndromic classification/endophenotype). Here we present a summary of the main genomic findings of these multidisciplinary studies, and discuss the importance, lessons, and challenges of genetic research of complex psychiatric disorders.

Envarsus, a novelty for transplant nephrologists: Observational retrospective study. / Envarsus, una novedad para los nefrólogos del trasplante: estudio observacional retrospectivo.

The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function. We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52years. The mean post-transplant time at the time of conversion to Envarsus was 76.3months and the mean follow-up in the Baseline and Conversion period was 10.1months and 11.6months, respectively. In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/mL (P=.636), with a mean daily dose that decreased significantly from 3mg to 2mg (P<.001), respectively, maintaining the filtration rate. The median Cptrough values in the Advagraf and Envarsus groups were 5.7ng/mL and 6.3ng/mL (P=.07), with a median daily dose of 7mg and 4mg (P<.001), respectively, and the same renal function. In stable renal transplant patients, the conversion from Advagraf to Envarsus has allowed the dose of tacrolimus to be reduced by 42.9% and, in the case of Prograf, by 33.3%, maintaining similar Cptrough values, without renal function being altered.

Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees.

We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.

Rediscovering the value of families for psychiatric genetics research.

As it is likely that both common and rare genetic variation are important for complex disease risk, studies that examine the full range of the allelic frequency distribution should be utilized to dissect the genetic influences on mental illness. The rate limiting factor for inferring an association between a variant and a phenotype is inevitably the total number of copies of the minor allele captured in the studied sample. For rare variation, with minor allele frequencies of 0.5% or less, very large samples of unrelated individuals are necessary to unambiguously associate a locus with an illness. Unfortunately, such large samples are often cost prohibitive. However, by using alternative analytic strategies and studying related individuals, particularly those from large multiplex families, it is possible to reduce the required sample size while maintaining statistical power. We contend that using whole genome sequence (WGS) in extended pedigrees provides a cost-effective strategy for psychiatric gene mapping that complements common variant approaches and WGS in unrelated individuals. This was our impetus for forming the "Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders" consortium. In this review, we provide a rationale for the use of WGS with pedigrees in modern psychiatric genetics research. We begin with a focused review of the current literature, followed by a short history of family-based research in psychiatry. Next, we describe several advantages of pedigrees for WGS research, including power estimates, methods for studying the environment, and endophenotypes. We conclude with a brief description of our consortium and its goals.